This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is the main research project in our laboratory where regulation of CART gene expression has been a focus. Because over expression of CREB in the N Acc reduces cocaine reward, and because injection of CART peptide into the N Acc reduces cocaine reward, we hypothesized that over expression of CREB in the N Acc should increase expression of CART peptide and found that CREB is an in vivo regulator of CART expression which appears to be a mechanism of the action of cocaine. CART peptide acts as a homeostatic regulator and tends to oppose the action of cocaine in the nucleus accumbens. Several other studies have shown: that administration of cocaine activates CART neurons in the N Acc [unreadable]which supports strongly an earlier proposal, that CART has a role in trabecular but not cortical bone mass as well as in the density of fat cells in bone marrow, and that estrogen and progesterone can affect CART levels in the midbrain in macaques. These latter studies continue to show the broad involvement of CART in a variety of physiological functions.